Morphine is the most abundant of at least 50 alkaloids found in opium, poppy and poppy derivatives, Papaver somniferum. Poppy straw is opium poppy (Poppy somniferum) that is harvested when fully mature and dry, minus the ripe poppy seeds. An agricultural by-product of the poppy seed harvest, the straw was a waste product before the 1930s when a chemical process became available to extract morphine from it. Poppy straw consisting mainly of the capsule became a valuable source of morphine. Today, poppy straw is a major source of many opioids and other alkaloids. It is the source of 90% of the world supply of legal morphine (i.e. for medical and scientific use).
During processing, poppy straw is pulverized and washed many times in water and/or various acids and other chemicals to produce poppy straw concentrate (PSC) or concentrated poppy straw (CPS). Once dried, the concentrate is a beige to brown colored powder and contains salts of various alkaloids. It can range from about 9 to 30 times the morphine concentration of poppy straw. Morphine is generally 8% to 17% of the dry weight of opium, although specially-designed cultivars reach 26% or produce little morphine at all. The latter varieties, including the Przemko and Norman strains of the opium poppy, are used to produce two other alkaloids, thebaine and oripavine, which are used in the manufacture of semi-synthetic opioids like oxycodone and etorphine as well as other types of drugs. At least one manufacturer, Tasmanian Alkaloids, produces both high-morphine and high-thebaine/oripavine types of CPS.
Morphine is produced most predominantly early in the life cycle of the plant and, past the optimum point for extraction, various processes in the plant produce codeine, thebaine, and in some cases low quantities of hydromorphone, dihydromorphine, dihydrocodeine, tetrahydrothebaine and hydrocodone.
Morphine, generally administered in a salt form, is a potent opiate analgesic, for the relief of moderate to severe pain, and has been approved for use for decades. It can be administered as an injectable solution, suppository, capsule, tablet or extended release product. Like other opioids, e.g. oxycodone, hydromorphone and diacetylmorphine (heroin), morphine acts directly on the central nervous system (CNS) to relieve pain. Today, morphine sulfate is sold under various trade names including Astramorph PF™, Avinza®, DepoDur®, Duramorph, Infumorph, Kadian®, MS-Contin®, Oramorph® SR and RMS. Kadian® is a morphine sustained-release dosage form for once or twice per day dosing. Kadian® is currently available in 10, 20, 30, 40, 50, 60, 80, 100 and 200 mg morphine sulfate extended release capsules.
Morphine is regarded as the opioid drug of choice in the treatment of cancer pain, for example. Side effects of morphine treatment include, for example, nausea and vomiting, constipation, sedation, confusion and loss of appetite. It has been suggested that the use of modified release morphine formulations, apart from their convenience and their ability to provide continuous analgesia, may also result in a lower incidence and severity of morphine-related side effects. Sustained-release morphine dosage forms are described in U.S. Pat. Nos. 5,202,128, 5,215,758, 5,378,474 and 5,672,360.
All references cited herein, including the morphine sulfate products associated with the above-mentioned trade names, are incorporated herein by reference in their entireties.